Harbored Human Papillomavirus DNA Research Articles

Prevalence of human papillomavirus in oral epithelial dysplasia: Systematic review and meta-analysis.

The purpose of this systematic review and meta-analysis was to estimate the overall and type-specific prevalence of human papillomavirus (HPV) DNA in oral epithelial dysplasia and assess p16INK4a overexpression in relation to HPV-status. A systematic literature search identified 31 eligible studies (832 cases) evaluating the presence of HPV DNA in oral epithelial dysplasia cases by PCR. Of these, six studies evaluated p16INK4a overexpression in relation to HPV-status. The overall pooled prevalence of HPV DNA in oral epithelial dysplasia was 27.2% (95% CI: 17.6-38.1). We observed substantial interstudy heterogeneity, which could not be explained by differences in continent, tissue type, or severity of epithelial dysplasia. HPV16 was the predominant genotype detected. Moreover, 62.2% of HPV positive and 17.8% of HPV negative oral epithelial dysplasia samples stained intensively positive for p16INK4a . This meta-analysis found that 27% of oral epithelial dysplasia harbor HPV DNA. Whether this represents a transient infection or has a carcinogenic role is unknown.

Prevalence of human papillomavirus16 DNA and p16INK4a protein in oral squamous cell carcinoma: A systematic review and meta-analysis.

Background and Aim:Indian patients with oral squamous cell carcinoma (OSCC) are etiologically associated with the use of tobacco and alcohol; yet, a proportion of tumors that may harbor human papillomavirus (HPV) infections cannot be neglected. The following meta-analysis was conducted to address the association of p16INK4a and HPV DNA with OSCC. In addition, the study also provides the updated prevalence of HPV-induced OSCC.Materials and Methods:Literature survey was performed using databases such as PubMed with the help of the following keywords – “HPV infection,” “oral squamous cell carcinoma,” “p16INK4a,” “HPV DNA,” “E6,” “E7,” “L1,” “L2” and “LCR.” Proportion method was performed to derive the forest plot using MedCalc statistical software version 16.4.3.Results:Among 145 research articles, 33 articles were selected for further analysis, in which 13 articles were related to HPV DNA detection in tissues, 11 articles detected the overexpression of p16INK4a and nine articles reported the detection of both HPV DNA and p16INK4a expression. Meta-analysis revealed significant heterogeneity (P < 0.0001) among the articles. Overall, the study consisted of 3339 patients with OSCC, among which 559 patients were diagnosed with the presence of HPV16 DNA with a random proportion of 20.1% at 95% confidence interval (CI) (13.9–27.1, P < 0.0001). Overexpression of p16INK4a protein was observed in 709 patients with a random proportion of 25.4% at 95% CI (14.3–38.3, P < 0.0001).Conclusion:HPV DNA and expression of p16INK4a was suggested as gold standard for the detection of HPV infection in many cases of cancers. Frequency of HPV infection is significantly higher in patients with OSCC as identified through the detection of HPV DNA and p16INK4a expression. Even though the association of HPV infection has been established in head and neck cancer, this review could further the establishment of molecular level interaction of HPV in patients with oral cancer.

Human papillomavirus in esophageal squamous cell carcinoma

Context: We studied the role of Human papillomavirus (HPV) in esophageal squamous cell carcinoma from North East India. Methods: Fifteen archival paraffin embedded esophageal squamous cell carcinoma tissues were retrieved. Thin sections were made to extract DNA from the tissues. HeLa cell lines which harbor HPV DNA were used as a positive control. Nested polymerase chain reaction (PCR) was performed to analyze the presence of HPV DNA. Amplified products were analyzed on a 2% agarose gel and visualized by ethidium bromide staining. Positive product was sequenced for confirmation of the result. Results: HPV DNA was not able to detect in any esophageal squamous cell carcinoma tissue. Positive control HeLa cells DNA was found to be positive for HPV DNA by nested PCR. Conclusions: Our study shows the negative association of HPV in esophageal squamous cell carcinoma. However, further studies are needed with a large number of sample size to rule out the role of HPV in this region.

Human papillomavirus prevalence and prognostic implication in oropharyngeal squamous cell carcinomas

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is associated with favorable survival. The purpose of this study was to evaluate the prevalence and prognostic significance of the HPV infection through both the p16 expression status and the oncogenic HPV DNA viral load. A retrospective chart review was conducted on all patients treated for oropharyngeal SCC between January 2007 and June 2009. P16 expression status by immunohistochemistry and HPV DNA viral load by quantitative polymerase chain reaction (qPCR) were evaluated on routine pretreatment tumor samples. One hundred thirty-three patients (94 men and 39 women) were included in the study. Mean age was 59 years. One hundred twenty-two lesions (92%) were localized to lymphoid areas. Sixty-seven patients (50%) were p16+, and 87 patients (65%) harbored HPV DNA. The p16+/HPV DNA+ profile (48%) was associated with the most favorable prognosis. HPV16 was responsible for the majority of the infections (89%). HPV is common among oropharyngeal SCC in France, and acts as an independent prognostic factor.

The role of human papillomavirus in head and neck cancer in Senegal

BackgroundExploring the presence and role of human papillomavirus (HPV) in head and neck cancer (HNC) is a necessary step to evaluate the potential impact of HPV prophylactic vaccines.ObjectiveTo assess the prevalence and oncogenic role of HPV in HNC in Senegal.MethodsThis is a multicenter cross-sectional study. Paraffin-embedded blocks of cases diagnosed with invasive HNC between 2002 and 2010 were collected from 4 pathology laboratories in Senegal. Presence of HPV DNA was determined by PCR and DEIA, and genotyping performed with LiPA25. Tubulin analysis was performed to assess DNA quality. HPV DNA-positive cases were tested for p16INK4a expression.FindingsA total of 117 cases were included in the analysis: 71% were men, mean age was 52 years old (SD ±18.3), and 96% of cases were squamous cell carcinoma. Analysis was performed on 41 oral cavity tumors, 64 laryngeal tumors, 5 oropharyngeal tumors and 7 pharyngeal tumors. Only four cases (3.4%; 95% CI = 0.9%-8.5%) harbored HPV DNA. HPV types detected were HPV16, HPV35 and HPV45. However, among HPV-positive cases, none showed p16INK4a overexpression.ConclusionOur findings indicate that HPV DNA prevalence in HNC in Senegal is very low, suggesting that HPV is not a strong risk factor for these cancers. Additional larger studies are needed to confirm these findings and explore other potential risk factors specific to the region.

Melanom Dışı Deri Kanserleri Gelişiminde Human Papillomavirüsün Rolü

Objective: Non-melanoma skin cancers (NMSC) represent the most frequent cancers among the Caucasian population worldwide. The possibility of the involvement of human pa - pillomavirus (HPV) in the development of these cancers is suggested by several studies. The pur - pose of this study is to evaluate the presence of various types of HPV in NMSC lesions of immunocompetent patients. Material and Methods: Biopsies taken from NMSC and non-sun ex - posed healthy skin from each of 32 immunocompetent patients were analysed for presence of HPV DNA by a polymerase chain reaction (PCR) using degenerate primers which can detect a broad spectrum of HPV types. Results: HPV DNA was detected in one of 21 basal cell carcino - mas, from one of two actinic keratosis and from none of 8 squamous cell carcinomas, and none of the control biopsy specimens. It was thought that in addition to factors associated with Turk - ish population, the specimens which were found to be HPV negative did not harbor HPV DNA, or although tissues harbor HPV DNA, it was not detected with the technique we used because of low viral load. Conclusion: We could not show an association between HPV infection and NMSC by using real-time PCR technique. Our data suggest that the use of MY09/MY11 primer pairs alone in PCR technique is not sufficient to evaluate the HPV prevalence in NMSC. We thought that studies with more patients and using more sensitive detection techniques which will be developed in the future are needed to show a significant association between HPV and NMSC

Alcohol, smoking and human papillomavirus in laryngeal carcinoma: a Nordic prospective multicenter study

Human papillomavirus (HPV) has been linked to oropharyngeal carcinomas, but its role in laryngeal squamous cell carcinoma (LSCC) is not clear. A prospective multicenter study based on known tumor-cell percentage of fresh frozen carcinoma biopsies was established to determine the HPV prevalence. Moreover risk factors such as smoking, alcohol abuse, chronic laryngitis and gastroesophageal reflux disease (GERD) were evaluated Fresh-frozen laryngeal cancer biopsies from 108 patients in Finland, Norway, and Sweden were investigated. Patients whose biopsy samples contained at least 20% tumor tissue (N = 69) entered the study. HPV DNA was determined with MY09/11 and GP5+/6+ nested PCR and SPF10 PCR hybridization assay. Patients were examined by an ENT specialist and an extensive questionnaire concerning risk factors was filled in. Only three patients (4.4%) harbored HPV DNA in their carcinoma sample. Heavy alcohol drinking was associated with an increased risk of death, advanced-stage disease, and younger age at diagnosis. Chronic laryngitis, GERD, and orogenital sex contacts were rare. Poor oral hygiene was not associated with survival, although it correlated with heavy drinking. In our series HPV was not important in LSCC. Heavy drinking led to major mortality in LSCC and promoted early carcinogenesis.

Presence of Human Papillomavirus DNA in Testicular Biopsies From Nonobstructive Azoospermic Men

Human papillomavirus (HPV) plays a major role in the etiology of many malignancies of diverse localization, such as uterine cervical carcinoma and its precursors. Human papillomavirus sequences have been detected throughout the male lower genitourinary tract, but the role of men as transmitters remains unclear. To investigate the relationship between azoospermia and the presence of HPV DNA in testicular cells. One hundred eighty-five patients with azoospermia undergoing testicular biopsy were studied. Histologic study was done on formalin-fixed, paraffin-embedded samples from testicular biopsies, stained with hematoxylin-eosin. Molecular study to detect HPV sequences was performed on genomic DNA isolated from paraffin sections by standard protocols. Seven cases containing HPV sequences were studied after microdissection with PALM microlaser technology in order to determine the presence of HPV DNA sequences in different cells, as well as from seminal tubules or stromal (Leydig) cells. Human papillomavirus DNA sequences were detected in testicular biopsies of 12 patients (6.48%). Human papillomavirus type 16 was the most common genotype encountered. Among the 92 patients who underwent bilateral testicular biopsy, HPV sequences were detected in 9 patients (9.78%), all of whom showed only unilateral testicular affection, more often in the left testicle (ratio, 2: 1). After microdissection, HPV DNA sequences were seen in Leydig and Sertoli cells; the presence of HPV in germinal cells could not be ruled out. Leydig cells, Sertoli cells, and probably germinal cells (cases 2, 3, and 4) harbored HPV DNA sequences. Such findings have not been previously described in testicular tissue.

Identification of human papillomavirus in keratoacanthomas.

Keratoacanthomas are benign, clinically distinct skin tumors that may infiltrate and show cellular atypia. A viral etiology has been suggested, and the aim was to search for human papillomavirus (HPV) in keratoacanthomas. From 21 immunosuppressed organ transplant recipients and 11 non-immunosuppressed patients, 72 fresh biopsies with diagnosis of keratoacanthomas were analyzed. For detection of cutaneous and genital HPV DNA, single-tube nested "hanging droplet" polymerase chain reaction (PCR) and another PCR (GP5+ and 6+) were used, respectively. Among 21 immunosuppressed patients, 71% (15/21) harbored HPV DNA at least in one sample. Of the keratoacanthoma lesions, 55% (33/60) were HPV DNA positive. Fourteen samples from eight immunosuppressed patients contained HPV types 5, 9, 10, 14, 19, 20, 21, 38, 49, 80, putative HPV types as HPVvs20-4, HPVvs75, and HPVvs92 and FA16.1, FA23.2, FA37, FA75, and FA81. Among 11 non-immunosuppressed patients, 36% (4/11) harbored HPV DNA at least in one sample, and 33% (4/12) of their keratoacanthomas were HPV DNA positive. In total, HPV DNA was detected in 51% (37/72) of the keratoacanthomas. By the use of PCR, cutaneous HPV DNA was detected in 51% (37/72) of the keratoacanthomas. No predominating HPV type or genital HPV type was identified. The role of HPV in keratoacanthomas remains thus elusive.

Vulvar Malignant Melanoma Associated With Human Papillomavirus DNA

Oncogenic human papillomavirus (HPV) types such as HPV 16 are known to play a crucial role in the development of anogenital carcinomas. The etiology of anogenital malignant melanoma is unknown. We report two case of vulvar malignant melanoma in which multiple HPV types including HPV 16 and putative novel HPV types (alb-1, alb-2, alb-7, and alb-10) were identified by degenerated nested polymerase chain techniques (polymerase chain reaction) in both the malignant melanoma and surrounding skin. One melanoma was associated with lichen sclerosus, and the other, with melanoma in situ and pigmented vulvar squamous papillomatosis. These melanomas harbored HPV types alb-7, and HPV 16 as well as alb-1, respectively. HPV types 16, 20, 21, 36, alb-2, and AJ001060 were detected in vulvar skin affected by lichen sclerosus. Vulvar squamous papillomatosis harbored HPV types 28 and alb-10. HPV 16 was physically integrated into the host genome in lichen sclerosus skin and possibly in the melanoma associated with pigmented vulvar squamous papillomatosis. Twenty-two percent (4 of 18) of normal control specimens from skin tumor excisions were found to harbor HPV DNA (HPV types 3, 54, and alb-7); none of these control samples harbored multiple HPV DNA. These findings of multiple HPV DNA and integrated HPV 16 in skin associated with vulvar malignant melanoma indicate that HPV may play a role in the development of vulvar malignant melanoma. The role of HPV could be either direct through infection of melanocytes or indirect as a cofactor with free radicals in chronic fibroinflammatory vulvar disorders such as lichen sclerosus.

Follow-up of human papillomavirus (HPV) DNA and local anti-HPV antibodies in cytologically normal pregnant women.

The high level of progesterone during pregnancy may enhance the transcription and replication of genital human papillomaviruses (HPV) through the glucocorticoid/progesterone response element found in the long control region of the viral genome. In this study, cytologically and colposcopically healthy pregnant women were subjected to a follow-up examination. Samples from the uterine cervix were collected during early pregnancy (n = 39), in the third trimester (n = 31), and a few weeks after birth (n = 30). The presence of HPV DNA was detected by polymerase chain reaction (PCR), while local secretory anti-viral IgA antibodies were demonstrated by enzyme-linked immunosorbent assay using synthetic peptide antigens. Follow-up examination by PCR revealed HPV DNA persistence in 5 women. In 5 other cases, HPV positivity changed from negative to positive during the follow-up. There was 1 case which changed from positive to negative and 1 in which the HPV type changed during the study. Altogether, 12 of 39 women (31%) were shown to harbor HPV DNA at some time during follow-up. HPV DNA positivity increased from 18% during early pregnancy to 27% after birth (difference not significant). On the other hand, there was a significant rise in the level of local antibodies against HPV antigens (E2, E7, and L2) between samples collected in early pregnancy and those collected after birth (P < 0.0001). This may indicate the reactivation of genital HPV infections during late pregnancy.

Socioeconomic differences in cervical cancer: two case-control studies in Colombia and Spain.

This study examined the causes of socioeconomic differences in invasive cervical cancer in two countries that differ substantially in cervical cancer incidence and economic development. Data were derived from two case-control studies carried out in Spain and Colombia; there were 373 case subjects, 387 control subjects, and 425 husbands interviewed with a structured questionnaire. Exfoliated cells were obtained from cervical or penile scrapes and tested for human papillomavirus (HPV) DNA. Relative to better educated women, women with low educational levels in both countries reported fewer Pap smears and had a higher prevalence of HPV DNA. The prevalence ratio of HPV DNA across educational strata was twofold in Spain and fourfold in Colombia. In both countries, husbands of poorly educated women reported higher use of prostitutes than husbands of better educated women. In Colombia, 30% of husbands of poorly educated women harbored HPV DNA, compared with 10% of husbands of better educated women. Socioeconomic differences in invasive cervical cancer could be partly explained by differences in the prevalence of HPV DNA and by a lower use of preventive care.

Histopathologic examination of penile epithelial lesions is of limited diagnostic value in human papillomavirus infection.

Guidelines for the histopathologic diagnosis of human papillomavirus (HPV) infection have been drawn from changes seen in cervical specimens not necessarily applicable to penile epithelium. To evaluate histopathologic examination as a means of diagnosing HPV infection of the male genital tract. Ninety-two consecutive male patients seen at the sexually transmitted diseases clinic. Twelve had condyloma acuminatum, and 80 had papular lesions, macular lesions, or both. Fifteen men without signs of HPV infection served as controls. Biopsy specimens were evaluated morphologically by light microscopy, and HPV DNA detection was performed by in situ hybridization and polymerase chain reaction. All acuminate lesions were HPV DNA positive with in situ hybridization. Forty papular and/or macular lesions harbored HPV DNA, 28 (35%) of them positive with in situ hybridization and the other 12 (15%) positive with polymerase chain reaction. Morphologic signs attributed to HPV infection were found in HPV-positive and HPV-negative penile lesions, as well as in normal epithelium. In papular and macular lesions, the only criterion associated with HPV DNA positivity was neoplastic changes, which was present in 16 (40%) HPV DNA-positive specimens, compared to 4 (10%) HPV DNA-negative specimens (P < 0.01). Of the 16 lesions with neoplasia, 15 (94%) had detectable HPV DNA of a potentially oncogenic type. Histopathologic signs of HPV infection other than neoplasia seem to be of limited value. Detection of the infectious agent, in this case HPV, should be the gold standard for the diagnosis as it is for other infectious diseases. The strong association between neoplasia and potentially oncogenic HPV types makes this issue even more important.

Human papillomavirus types 11 and 16 detected in nasopharyngeal carcinomas by the polymerase chain reaction.

Most nasopharyngeal carcinomas (NPCs) are of the nonkeratinizing or undifferentiated types, which are consistently associated with Epstein-Barr virus (EBV). The smaller group of highly differentiated, keratinizing NPCs seems to be only infrequently associated with EBV. In order to examine whether these rare tumors were related to another oncogenic virus, the authors used the polymerase chain reaction to examine paraffin-embedded sections of 15 keratinizing NPCs for human papillomavirus (HPV) types 6, 11, 16, and 18 genomic sequences. HPV DNA was found in 4 tumors (1 HPV-11-positive, and 3 HPV-16-positive tumors). None of 23 undifferentiated or nonkeratinizing NPCs harbored HPV DNA. The putatively oncogenic HPV type 16 may thus be involved in the carcinogenesis of some EBV-negative keratinizing squamous cell nasopharyngeal carcinomas.

Detection of human papillomavirus infection in diseased and nondiseased sites of the respiratory tract in recurrent respiratory papillomatosis patients by DNA hybridization.

We examined 12 recurrent respiratory papillomatosis patients, who were undergoing treatment for recurrence of their disease, for the presence of human papillomavirus (HPV). Biopsies were obtained from their respiratory papillomas and nondiseased sites (NDS) of the respiratory tract: the nasopharynx, posterior tonsillar pillar, aryepiglottic fold, cervical trachea, intrathoracic trachea, and bronchi. The presence of HPV DNA was determined by using the ViraPap/ViraType DNA hybridization procedure. Two thirds of the patients were infected with HPV 6/11 in either the diseased papilloma or NDS: 50% of patients with papilloma specimens typed positive (6 of 12), and 40% of the patients typed HPV-positive in one or more biopsies from the NDS (4 of 10). No single NDS was more likely to be infected with HPV than any other. No oncogenic HPV types 16/18 or 31/33/35 were detected in the papillomas or NDS of these patients. Only patients with multiple, and not isolated, papilloma involvement were found to harbor HPV DNA in NDS; and 80% of those with infected NDS, compared to 20% of those without infected NDS, required a shorter (no more than 3 months) surgical treatment interval. Our results show that HPV infection frequently persists in adjacent, clinically normal sites, and suggest that the extent of NDS involvement may predict both the extent of disease and the likelihood of recurrence.

Detection of human papillomavirus (HPV) DNA in focal epithelial hyperplasia

Five focal epithelial hyperplasia (FEH) specimens from four patients were examined by Southern blot hybridization analysis to determine the specific human papillomavirus (HPV) types present. The histomorphologic features of these specimens were also evaluated and a broad variety of changes including koilocytes, mitosoid cells, ballooning cells and cells showing individual cell keratinization were noted. FEH lesions from the three patients sharing a familial relationship demonstrated HPV DNA sequences that were either the prototype HPV-13 or a very closely related HPV-13 subtype. These patients also showed similar clinical features. Lesional tissue from the other patient was found to harbor HPV DNA sequences similar to HPV-32. In view of these findings it is suggested that these specific HPV types are associated with the characteristic FEH histomorphology described.